A 35-year follow-up study of patients admitted to methadone treatment between 1982-1984 in Asturias, Spain

Authors

  • Luis Jiménez-Treviño Universidad de Oviedo Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) Servicio de Salud del Principado de Asturias (SESPA) Instituto de Neurociencias del Principado de Asturias (INEUROPA)
  • Clara Martínez-Cao Universidad de Oviedo Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) Instituto de Neurociencias del Principado de Asturias (INEUROPA)
  • Fernando Sánchez-Lasheras Tecniproject S.L.
  • Celso Iglesias Universidad de Oviedo Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) Servicio de Salud del Principado de Asturias (SESPA) Instituto de Neurociencias del Principado de Asturias (INEUROPA)
  • María Jesús Antuña Servicio de Salud del Principado de Asturias (SESPA)
  • Leonor Riera Instituto de Neurociencias del Principado de Asturias (INEUROPA)
  • Pilar Alejandra Sáiz-Martínez Universidad de Oviedo Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) Servicio de Salud del Principado de Asturias (SESPA) Instituto de Neurociencias del Principado de Asturias (INEUROPA)
  • Julio Bobes Universidad de Oviedo Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) Servicio de Salud del Principado de Asturias (SESPA) Instituto de Neurociencias del Principado de Asturias (INEUROPA)

DOI:

https://doi.org/10.20882/adicciones.1662

Keywords:

Mortality, heroin addiction, methadone maintenance therapy, follow-up.

Abstract

The objective was to evaluate outcomes in a heroin-dependent population 35 years after first enrolment in methadone maintenance treatment (MMT).  An ad hoc protocol was used to assess drug misuse, treatment, and drug-related morbidity in the survivor sample. The standardized mortality ratio (SMR) and 95% confidence interval (CI) were calculated.  A total of 214 heroin-dependent patients entered MMT between 1982 and 1984 in the Asturias Public Health Service. Information was received on 195 subjects, of whom 146 were deceased.  Men accounted for 77.5% of the study cohort. Over the 35-year follow-up period, the SMR was 11.75 (95% CI = 9.95 – 13.77). In the survivor sample, 5.7% were still enrolled in MMT; human immunodeficiency virus (HIV) was diagnosed in 38.77% and hepatitis B/C in 73.46%. No differences were found between sexes in mortality or HIV and hepatitis B/C status. None of the female survivors were using heroin at the 35-year follow-up compared with 5.26% of males. In conclusion, our study confirms the high long-term mortality rate of heroin addicts, even after enrollment in MMT. 

Author Biographies

Luis Jiménez-Treviño, Universidad de Oviedo Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) Servicio de Salud del Principado de Asturias (SESPA) Instituto de Neurociencias del Principado de Asturias (INEUROPA)

Área de Psiquiatría

Clara Martínez-Cao, Universidad de Oviedo Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) Instituto de Neurociencias del Principado de Asturias (INEUROPA)

Área de Psiquiatría

Fernando Sánchez-Lasheras, Tecniproject S.L.

Research Department

Celso Iglesias, Universidad de Oviedo Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) Servicio de Salud del Principado de Asturias (SESPA) Instituto de Neurociencias del Principado de Asturias (INEUROPA)

Área de Psiquiatría

Pilar Alejandra Sáiz-Martínez, Universidad de Oviedo Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) Servicio de Salud del Principado de Asturias (SESPA) Instituto de Neurociencias del Principado de Asturias (INEUROPA)

Área de Psiquiatría

Julio Bobes, Universidad de Oviedo Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) Servicio de Salud del Principado de Asturias (SESPA) Instituto de Neurociencias del Principado de Asturias (INEUROPA)

Área de Psiquiatría

References

Adelson, M., Wilson, H. W., Celeste, V. Y. M., Linzy, S., Kreek, M. J. y Peles, E. (2013). Methadone maintenance treatment experience in Macao–prospective follow-up for initial 4.5 years. Journal of Psychoactive Drugs, 45, 313-321. doi:10.1080/02791072.2013.825032.

Bauer, S. M., Loipl, R., Jagsch, R., Gruber, D., Risser, D., Thau, K.,… Fischer, G. (2008). Mortality in opioid-maintained patients after release from an addiction clinic. European Addiction Research, 14, 82–91. doi:10.1159/000113722.

Berenguer, J. (2018). Elimination of Hepatitis C Virus in Spain: A pending challenge. Enfermedades Infecciosas y Microbiología Clínica, 36, 323-324. doi:10.1016/j.eimc.2018.03.001.

Buti, M., Calleja, J. L., García-Samaniego, J., Serra, M. Á., Crespo, J., Romero, M.,… Razavi, H. (2017). Elimination of hepatitis C in Spain: Adaptation of a mathematical model based on the public health strategic plan for addressing hepatitis C in the National Health System. Medicina Clínica, 148, 277–282. doi:10.1016/j.medcli.2016.12.018.

Clausen, T., Anchersen, K. y Waal, H. (2008). Mortality prior to, during and after opioid maintenance treatment (OMT): A national prospective cross-registry study. Drug and Alcohol Dependence, 94, 151-157. doi:10.1016/j.drugalcdep.2007.11.003.

Cousins, G., Boland, F., Courtney, B., Barry, J., Lyons, S. y Fahey, T. (2016). Risk of mortality on and off methadone substitution treatment in primary care: A national cohort study. Addiction, 111, 73-82. doi:10.1111/add.13087.

Cowie, M. R., Blomster, J. I., Curtis, L. H., Duclaux, S., Ford, I., Fritz, F.,… Zalewski, A. (2017). Electronic health records to facilitate clinical research. Clinical Research in Cardiology: Official Journal of the German Cardiac Society, 106, 1–9. doi:10.1007/s00392-016-1025-6.

Darke, S., Mills, K. L., Ross, J. y Teesson, M. (2011). Rates and correlates of mortality amongst heroin users: Findings from the Australian treatment outcome study (ATOS), 2001–2009. Drug and Alcohol Dependence, 115, 190-195. doi:10.1016/j.drugalcdep.2010.10.021.

Davstad, I., Stenbacka, M., Leifman, A. y Romelsjö, A. (2009). An 18-year follow-up of patients admitted to methadone treatment for the first time. Journal of Addictive Diseases, 28, 39–52. doi:10.1080/10550880802544997.

Degenhardt, L., Bucello, C., Mathers, B., Briegleb, C., Ali, H., Hickman, M. y McLaren, J. (2011). Mortality among regular or dependent users of heroin and other opioids: A systematic review and meta-analysis of cohort studies. Addiction, 106, 32-51. doi:10.1111/j.1360-0443.2010.03140.x.

Dole, V.P. (2008). Implications of methadone maintenance for theories of narcotic addiction. Journal of the American Medical Association, 260, 3025-3029.

Dole, V.P., Nyswander, M.E. y Kreek, M.J. (1966). Narcotic blockade. Archives of Internal Medicine, 118, 304-309.

Dunn, K.E., Finan, P.H., Tompkins, D. A. y Strain, E.C. (2018). Frequency and correlates of sleep disturbance in methadone and buprenorphine-maintained patients. Addictive Behaviors, 76, 8-14. doi:10.1016/j.addbeh.2017.07.016.

European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) (2019). EMCDDA—Information on drugs and drug addiction in Europe. http://www.emcdda.europa.eu/.

Esteban, J., Gimeno, C., Barril, J., Aragonés, A., Climent, J. M. y de la Cruz Pellín, M. (2003). Survival study of opioid addicts in relation to its adherence to methadone maintenance treatment. Drug and Alcohol Dependence, 70, 193-200. doi:10.1016/s0376-8716(03)00002-4.

Evans, E., Li, L., Min, J., Huang, D., Urada, D., Liu, L.,… Nosyk, B. (2015). Mortality among individuals accessing pharmacological treatment for opioid dependence in California, 2006–10. Addiction, 110, 996-1005. doi:10.1111/add.12863.

Finkelstein, D. M., Muzikansky, A. y Schoenfeld, D. A. (2003). Comparing survival of a sample to that of a standard population. Journal of the National Cancer Institute, 95, 1434–1439. doi:10.1093/jnci/djg052.

Fridell, M., Bäckström, M., Hesse, M., Krantz, P., Perrin, S. y Nyhlén, A. (2019). Prediction of psychiatric comorbidity on premature death in a cohort of patients with substance use disorders: A 42-year follow-up. BMC Psychiatry, 19, 150. doi:10.1186/s12888-019-2098-3.

Haastrup, S. y Jepsen, P.W. (1988). Eleven-year follow-up of 300 young opioid addicts. Acta Psychiatrica Scandinavica, 77, 22-26. doi:10.1111/j.1600-0447.1988.tb05071.x.

Hall, W., Lynskey, M. y Degenhardt, L. (2002). Trends in opiate-related deaths in the United Kingdom and Australia, 1985–1995. Drug and Alcohol Dependence, 57, 247–254. doi:10.1016/s0376-8716(99)00057-5.

Hernando, V., Perez-Cachafeiro, S., Lewden, C., Gonzalez, J., Segura, F., Oteo, J. A.,… CoRIS. (2012). All-cause and liver-related mortality in HIV positive subjects compared to the general population: Differences by HCV co-infection. Journal of Hepatology, 57, 743–751. doi:10.1016/j.jhep.2012.06.010.

Holland, R., Maskrey, V., Swift, L., Notley, C., Robinson, A., Nagar, J.,… Kouimtsidis. (2013). Treatment retention, drug use and social functioning outcomes in those receiving 3 months versus 1 month of supervised opioid maintenance treatment. Results from the super C randomized controlled trial. Addiction, 109, 596-607. doi:10.1111/add.12439.

Hser, Y. I., Evans, E., Grella, C., Ling, W. y Anglin, D. (2015). Long-term course of opioid addiction. Harvard Review of Psychiatry, 23, 76-89. doi:10.1097/HRP.0000000000000052.

Hser, Y.I., Hoffman, V., Grella, C.E. y Anglin, M.D. (2001). A 33-year follow-up of narcotics addicts. Archives of General Psychiatry, 58, 503–508. doi:10.1001/archpsyc.58.5.503.

Instituto Nacional de Estadística. (2018). Defunciones según causa de muerte. Año 2018. https://www.ine.es/dyngs/INEbase/es/operacion.htm?c= Estadistica_C&cid=1254736176780&menu=ultiDatos&idp=1254735573175.

Jimenez, L., Saiz, P. A., Gutierrez, E., Bascaran, M. T., Carreño, E. y González-Quiros, M. (2000). Valoración transversal tras quince años en una muestra de adictos a opiáceos en Asturias. Adicciones, 12, 507–513.

Jimenez-Treviño, L., Saiz, P. A., García-Portilla, M. P., Díaz-Mesa, E. M., Sánchez-Lasheras, F., Burón, P.,… Bobes, J. (2011). A 25-year follow-up of patients admitted to methadone treatment for the first time: Mortality and gender differences. Addictive Behaviors, 36, 1184-1190. doi:10.1016/j.addbeh.2011.07.019.

Kleber, H. D. (2008). Methadone maintenance 4 decades later: Thousands of lives saved but still controversial. Journal of the American Medical Association, 300, 2303–2305. doi:10.1001/jama.2008.648.

Levine, O.S., Vlahov, O., Koehler, J., Cohn, S., Spronk, A.M. y Nelson, K.E. (1995). Seroepidemiology of hepatitis B virus in a population of injecting drug users. Association with drug injection patterns. American Journal of Epidemiology, 142, 331-341. doi:10.1093/oxfordjournals.aje.a117639.

Lin, C., Wu, Z. y Detels, R. (2011). Opiate users’ perceived barriers against attending methadone maintenance therapy: A qualitative study in china. Substance Use and Misuse, 46, 1190–1198. doi:10.3109/10826084.2011.561905. 

Maremmani, A. G., Pallucchini, A., Rovai, L., Bacciardi, S., Spera, V., Maiello, M.,... Maremmani, I. (2018). The long-term outcome of patients with heroin use disorder/dual disorder (chronic psychosis) after admission to enhanced methadone maintenance. Annals of General Psychiatry, 17, 14. doi:10.1186/s12991-018-0185-3.

Marotta, P. L. y McCullagh, C. A. (2017). A cross-national analysis of the association between years of implementation of opioid substitution treatments and drug-related deaths in Europe from 1995 to 2013. European Journal of Epidemiology, 33, 679-688. doi:10.1007/s10654-017-0342-z.

Mattick, R.P., Breen, C., Kimber, J. y Davoli, M. (2009). Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database of Systematic Reviews, 3, 1-32. doi:10.1002/14651858.CD002209.pub2.

Motta-Ochoa, R., Bertrand, K., Arruda, N., Jutras-Aswad, D. y Roy, E. (2017). “I love having benzos after my coke shot”: The use of psychotropic medication among cocaine users in downtown Montreal. International Journal of Drug Policy, 49, 15–23. doi:10.1016/j.drugpo.2017.07.012.

Nehkant, H., Rathod, W., Addenbrooke, M. y Rosenbach, A.F. (2005). Heroin dependence in an English town: 33-year follow-up. British Journal of Psychiatry, 18, 421-425. doi:10.1192/bjp.187.5.421.

Nordmann, S., Lions, C., Vilotitch, A., Michel, L., Mora, M., Spire, B.,… ANRS Methaville study group. (2016). A prospective, longitudinal study of sleep disturbance and comorbidity in opiate dependence (the ANRS Methaville study). Psychopharmacology, 233, 1203-1213. doi:10.1007/s00213-016-4202-4.

Nosyk, B., Min, J. E., Evans, E., Li, L., Liu, L., Lima, V. D.,… Montaner, J.S.G. (2015). The effects of opioid substitution treatment and highly active antiretroviral therapy on the cause-specific risk of mortality among HIV-positive people who inject drugs. Clinical Infectious Diseases, 61, 1157-1165. doi:10.1093/cid/civ476.

Novick, D. M., Richman, B. L., Friedman, J. M., Friedman, J. E., Fried, C., Wilson, J. P.,… Kreek, M.J. (1993). The medical status of methadone maintenance patients in treatment for 11–18 years. Drug and Alcohol Dependence, 33, 235-245. doi:10.1016/0376-8716(93)90110-c.

Nyhlén, A., Fridell, M., Bäckström, M., Hesse, M. y Krantz, P. (2011). Substance abuse and psychiatric co-morbidity as predictors of premature mortality in Swedish drug abusers: A prospective longitudinal study 1970-2006. BMC Psychiatry, 11, 122. doi:10.1186/1471-244X-11-122.

Oppenheimer, E., Tobutt, C., Taylor, C. y Andrew, T. (1994). Death and survival in a cohort of heroin addicts from London clinics: A 22-year follow-up study. Addiction, 89, 1299–1308. doi:10.1111/j.1360-0443.1994.tb03309.x.

Potik, D., Abramsohn, Y., Schreiber, S., Adelson, M. y Peles, E. (2020). Drug abuse and behavioral transgressions during methadone maintenance treatment (MMT) are related to high psychopathy levels. Substance Use & Misuse, 55, 460-468. doi:10.1080/10826084.2019.1685546.

R Core Team (2019). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/.

Randesi, M., Van den Brink, W., Levran, O., Blanken, P., Butelman, E. R., Yuferov, V.,… Kreek, M.J. (2016). Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence. Drug and Alcohol Dependence, 168, 164-169. doi:10.1016/j.drugalcdep.2016.08.634.

Ravndal, E. y Vaglum, P. (1998). Psychopathology, treatment completion and 5 years outcome. A prospective study of drug abusers. Journal of Substance Abuse Treatment, 15, 135–142.

Rehm, J., Frick, U., Hartwig, C., Gutzwiller, F., Gschwend, P. y Uchtenhagen, A. (2005). Mortality in heroin-assisted treatment in Switzerland 1994-2000. Drug and Alcohol Dependence, 79, 137–143. doi:10.1016/j.drugalcdep.2005.01.005.

Russolillo, A., Moniruzzaman, A. y Somers, J. M. (2018). Methadone maintenance treatment and mortality in people with criminal convictions: A population-based retrospective cohort study from Canada. PLoS Medicine, 15. doi:10.1371/journal.pmed.1002625.

Sammet, J.H., Walley, A.Y. y Bridden, C. (2007). Illicit drugs, alcohol, and addiction in human immunodeficiency virus. Panminerva Medica, 49, 67-77.

Sánchez-Carbonell, X. y Seus, L. (2000). Ten-year survival analysis of a cohort of heroin addicts in Catalonia: The EMETYST project. Addiction, 95, 941–948. doi:10.1046/j.1360-0443.2000.95694110.x.

Segest, E., Mygind, O. y Bay, H. (1990). The influence of prolonged stable methadone maintenance treatment on mortality and employment: An 8-year follow-up. International Journal of the Addictions, 25, 53–63.

Sordo, L., Barrio, G., Bravo, M. J., Indave, B. I., Degenhardt, L., Wiessing, L.,... Pastor-Barriuso, R. (2017). Mortality risk during and after opioid substitution treatment: Systematic review and meta-analysis of cohort studies. British Medical Journal, 357, 1550. doi:10.1136/bmj.j1550.

Soyka, M., Strehle, J., Rehm, J., Bühringer, G. y Wittchen, H. U. (2017). Six-year outcome of opioid maintenance treatment in heroin-dependent patients: Results from a naturalistic study in a nationally representative sample. European Addiction Research, 23, 97-105. doi:10.1159/000468518.

Stenbacka, M., Leifman, A. y Romelsjö, A. (2010). Mortality and cause of death among 1705 illicit drug users: A 37 year follow up. Drug and Alcohol Review, 29, 21-27. doi:10.1111/j.1465-3362.2009.00075.x.

Sutlovic, D., Kljucevic, Z., Sliskovic, L., Susnjar, H., Viskovic, I. y Definis-Gojanovic, M. (2018). Methadone maintenance treatment: A 15-year retrospective study in Split-Dalmatia County, Croatia. Therapeutic Drug Monitoring, 40, 486-494. doi:10.1097/FTD.0000000000000519.

Wang, K., Fu, H., Longfield, K., Modi, S., Mundy, G. y Firestone, R. (2014). Do community- based strategies reduce HIV risk among people who inject drugs in China? A quasi-experimental study in Yunnan and Guangxi provinces. Harm Reduction Journal, 6, 11-15. doi:10.1186/1477-7517-11-15.

Ward, J., Hall, W. y Mattick, R.P. (1999). Role of maintenance treatment in opioid dependence. Lancet, 353, 221–226. doi:10.1016/S0140-6736(98)05356-2.

Zhou, K. y Zhuang, G. (2014). Retention in methadone maintenance treatment in mainland China, 2004–2012: A literature review. Addictive Behaviors, 39, 22-29. doi:10.1016/j.addbeh.2013.09.001.

Published

2021-11-23

Issue

Section

Originals